Transcript Lipid Metabolizması

Fat catabolism: generation of energy by fatty acid oxidation
Fat (triacylglycerol) and Fatty Acids: 90% of dietary lipids are tryacylglycerol, a
hydrophobic, neutral molecule made from reaction of OH group of glycerol and
COO- group of fatty acids.
Fatty acids are made up of a long hydrophobic hydrocarbon chain (highly
reduced) and a carboxylic acid polar group. Different kinds of fatty acids play
very important structural (as major component of membrane structures) and
functional role.
In this part of discussion we will mainly focus of the digestion, transport and
catabolism of triglycerides. Although other lipids like cholesterol, sphingolipids
are important too but they will not be covered in this course.
Sources of Fat available for oxidation: 1. Dietary fat, 2. Excess dietary fat stored
in adipose tissue and 3. Excess carbohydrate calories are converted to FAT in
liver and transported to adipose tissues.
Function:
-Stored fat acts as major energy source when there is no carbohydrate available,
-it also serves as source for supply of fatty acids required for important cellular
function
provide insulation and complexion to body
Michael Cooper Has cut
his calorie intake to
nearly half of the daily
requirement.
He does not have any fat
storage, thus he faces
the following problems;
1. Looks sick: bad
complexion or look
2. He feels terribly cold
even at 20 oC: no
insulation.
3. Cannot afford to
starve even for a few
days; no fat store to
sustain survival.
Different kinds of
lipids
We will focus on
catabolism of
storage lipids.
Cholesterol plays an
important role in
transport and
metabolism of
lipids.
Tri-acylglycerols (fat) molecules are highly hydrophobic. After ingestion they are
present in the form of oil droplets. In order to get digested and absorbed, they
need to be emulsified (partially solubilized.
Liver produces bile acids which are collected in gall bladder and released into
intestine, where they in emulsification of fat.
Bile acids are amphipathic, detergent like molecules capable of binding to
hydrophobic as well as hydrophilic molecules.
Some important players involved in lipid digestion and transport:
Bile Acids: These are amphiphathic (with polar and non-polar structures)
detergent like molecules synthesized in liver. They help solubilize or emulsify
the triglycerides (fat) in the small intestine.
Pancreatic Lipases: These are pancreatic enzymes that catalyze the
hydrolysis of fat to release fatty acids and glycerol in intestine.
Bile acid and Fatty acid binding proteins: They facilitate absorption of
lipids in intestine.
Intestinal Fatty acid binding proteins (I-FABP): these proteins are present
inside the intestinal cells, they bind to fatty acids and protect cells from the
detergent like behavior of fatty acids.
Chylomicrons: These are lipoprotein granules containing specific
lipoproteins, dietary cholesterol, phospholipids and triacylglycerol. These
transport granules transport cholesterol and lipids from intestine to adipose
tissues and liver via blood.
Lipoprotein lipase: These enzymes are present in the capillaries of the
peripheral tissues. They digest triglycerides into Fatty acid and glycerol.
Lipid Transport:
Chylomicrons transport cholesterol and lipids from intestine to adipose
tissues and liver via blood.
Very low density lipoproteins (VLDL): are synthesized in liver and transport
endogenous triacylglycerol and cholesterol from liver to adipose and muscle
tissue. Capilary lipoprotein lipases degrade VLDL and fatty acid and glycerol
are delivered to adipocytes or muscle.
After giving up their triacylglycerols, the VLDL remnants appear in the blood
as Intermediate density lipoproteins (IDL) and then as low density
lipoproteins (LDL).
IDL and LDLs are taken back by liver by specific receptor mediated
endocytosis.
High density lipoproteins (HDL) are assembled from the degradation
products of other lipoproteins. HDLs mop up excess cholesterol from other
tissues and deliver it to liver.
Utilization of stored fat
•Low blood glucose and energy
need trigger the secretion of
epinephrine and glucagon
hormones
•Activation of adnylate cyclase
•Production of cAMP
•Activation of cAMP-dependent
protein kinase
•Phosphorylation and activation
of triacylglycerol lipase
•Release of fatty acids in blood
and binding of fatty acids to
serum albumin
•Transport of FA through serum
albumin to the muscle tissues
•B-oxidation of FA to produce
acetyl CoA.
Catabolism of glycerol after
lipase reaction:
After the triacylglycerol (fat) is
digested by lipase, it releases
fatty acids, and glycerol.
Glycerol can be converted to
glycerol 3 phosphate and then
to dihydroxy acetone
phosphate (DHAP).
DHAP is converted to
Glyceraldehyde 3 P by triose
phosphate isomerase (reaction
# 5) which enters the GAPDH
reaction (reaction # 6)of
glycolysis directly.